3-Methoxytyramine can only be formed from released dopamine (DA). It is the major metabolite of released DA in the rat brain. For this reason, measurements of central 3MT concentration and/or turnover rate in the brains can yield important information on the way central DA neuronal systems function in both normal controls and the mentally ill. Although postmortem brain tissue, 3MT, is a good index of DA release, one could argue that it may not faithfully represent the true dynamics of DA release as opposed to extracellular measures of DA concentrations by microdialysis. Furthermore, since measuring CSF concentrations of DA metabolites is the most convenient and practical approach to assessing central DA neuronal activities in man, there is a need to evaluate how representative of DA release DOPAC and HVA are, as opposed to 3MT. We have therefore compared microdialysate concentrations of 3MT and DA after electrical stimulation of the midforebrain bundle of the same rats. We have also measured changes in 3MT in the CSF of humans before and after the administration of neuroleptics and compared the changes with those of DOPAC and HVA. To gain a better understanding of the heterogeneity of brain DA neuronal activities, we have also compared and contrasted the effects of a number of psychostimulants on brain regional concentrations of 3MT.